FREE RADICALS & DISEASE!

Degenerative Diseases caused by Free Radicals

Free radicals in the genesis of Alzheimer's diseaseJ. S. Richardson - Department of Pharmacology, College of Medicine, University of Saskatchewan, Saskatoon, Canada.
As part of an ongoing investigation of the role of oxygen free radicals in Alzheimer's disease (AD), the formation of peroxidation products,
the activities of free radical defense enzymes, and the level of total iron were determined in autopsy brain tissue from donors with AD and
from age-matched non-demented donors. Calcium uptake was also investigated in mitochondria harvested from fibroblasts grown in tissue culture
from skin samples taken from brain donors. Compared to controls, homogenates of AD frontal cortex produced elevated levels of peroxidation
products and this difference was amplified in a dose-dependent manner by iron (1 to 200 microM). Peroxidation produced by 200 microM iron was
reduced dose dependently by the lazaroid U-74500A. The IC50 was 10 microM in AD cortex and 2.5 microM in controls. Superoxide dismutase
(SOD), one of the free radical defensive enzymes, was reduced by 25 to 35% in AD frontal cortex, hippocampus and cerebellum. In other brain
areas, SOD did not differ between AD and control. The activities of catalase and glutathione peroxidase were the same in AD and control
samples. Endogenous iron levels were higher in AD frontal cortex (2.5 nmol/mg protein) than in controls (1.5 nmol/mg protein). Calcium uptake
by AD fibroblast mitochondria is 50% lower than in controls under basal conditions. Following exposure to 200 microM iron, mitochondrial
calcium uptake is increased by 58% in AD and by 38% in controls. Pretreatment with 200 microM U-74500A or 1 mM deferoxamine, prior to
exposure to 200 microM iron, gave complete protection to control mitochondria but gave only partial protection to AD mitochondria. These
studies indicate that in AD, both CNS and peripheral cells show increased sensitivity to oxygen free radicals. The source of this increased
sensitivity has not yet been identified but could reflect either reduced free radical defenses or increased free radical formation or both.
Work is underway using electron paramagnetic resonance spectrometry to determine in vivo, premortem free radical activity in AD patients.

Free radical oxidative damage and Alzheimer's disease EE Tuppo; LJ Forman
There is increasing evidence that free radical-induced oxidative damage may play a role in the pathogenesis of Alzheimer's disease. Free
radicals are reactive oxygen compounds that may attack and damage lipids, proteins, and DNA. The brain is especially sensitive to oxidative
damage because of its high content of readily oxidized fatty acids, high use of oxygen, and low levels of antioxidants. Evidence for
oxidative damage has been obtained from postmortem brain tissue as well as from living patients with Alzheimer's disease. Antioxidants such
as vitamin E show promise that they may help in treating the disease.

Prospects for the prevention of free radical disease, regarding cancer and cardiovascular disease K F Gey - Vitamin Unit, Institute of Biochemistry and Molecular Biology, University of Berne Berne, Switzerland (Abstract)
Free radicals may be involved in the aetiology of cancer and cardiovascular diseases. In epidemiological studies poor plasma levels of all
essential antioxidants are associated with increased relative risks; in particular, low levels of carotene and vitamin E with the risk of
cancer and ischemic heart disease, respectively. The studies suggest that for optimal synergistic protection the plasma antioxidant levels
should simultaneously exceed the threshold values of 28–30 µmol/l lipid-standardized vitamin E, 40–50 µmol/l vitamin C, 0.4–0.5
(µmol/l carotene and 2.2–2.8 µmol/l lipid-standardized vitamin A. However the preventive efficacy of an optional antioxidant status is still
to be proven in randomized intervention trials. Although these antioxidant micronutrients may be the primary protective components of
vegetable-rich ‘preventive’ diets, the potentials of other plant components await exploration, eg carotenoids other than ß-carotene,
bioflavonoids and oxygen-sensitive B-vitamins.

The role of free radicals in muscular dystrophy James G. Tidball1* and Michelle Wehling-Henricks2 - 1 Department of Physiological Science, University of California - Los Angeles, Los Angeles, California, United States
2 Department of Physiological Science, University of California - Los Angeles, 90095, California, United States
Null mutation of members of the dystrophin protein complex can cause progressive, and possibly fatal, muscle wasting. Although these muscular
dystrophies arise from mutation of a single gene that is expressed primarily in muscle, the resulting pathology is complex and multi-systemic.
Prior to the identification of the deficient proteins that underlie muscular dystrophies such as Duchenne muscular dystrophy (DMD), oxidative
stress was proposed as a major cause of the disease. Now, current knowledge indicates that interactions between the primary genetic defect
and disruptions in the production of free radicals contribute these diseases. In this review, we focus on the pathophysiology of
dystrophin-deficiency in humans with DMD and the mdx mouse model of DMD. Current evidence indicates three routes through which free radical
production can be disrupted in dystrophin-deficiency and promote pathology. First, constitutive differences in free radical production can
disrupt signaling in muscle and other tissues and exacerbate pathology. Second, tissue responses to the pathology can shift free radical
production to promote cellular injury and dysfunction. Finally, behavioral differences in the affected individual can cause changes in the
production free radicals and contribute to disease. Unfortunately, the complexity of the free radical mediated processes that are perturbed
in muscular dystrophy makes it difficult to develop therapies founded on systemic administration of anti-oxidants. More mechanistic knowledge
of the specific disruptions of free radicals that underlie major features of muscular dystrophy is needed to develop more targeted therapeutic
approaches.

Iron, Free Radicals and Oxidative InjuryJoe M McCord, University of Colorado Health Sciences Center, Denver, Colorado
The ability of transition metal ions to undergo facile 1-electron oxidation or reduction makes them obvious potential chemical partners for
reactions involving biological free radicals. It is not coincidental that superoxide dismutases, the enzyme that catalytically destroy, the
superoxide radical (O2) by alternately oxidising and reducing it, have been found containing 3 transition metals (Cu, Mn or Fe) at
their active sites. Iron is by far the most abundant transition metal in the human body because of its roles in oxygen binding and transport
and electron transport. It provides opportunites for the cause of diseases related to iron absorption, transport and metabolism as well as
for the excerbation of mechanisms of disease involving free radical injury

Oxygen-derived free radicals and postischemic myocardial dysfunction ("stunned myocardium")R. Bolli, Department of Medicine, Baylor College of Medicine, Houston, Texas
Experimental studies have demonstrated that myocardium reperfused after reversible ischemia exhibits prolonged depression of contractile
function ("stunning"), which is associated with various ultrastructural, biochemical, vascular and other functional abnormalities. Clinical
observations suggest that stunning occurs in many situations (for example, rest and exercise-induced angina, myocardial infarction with early
reperfusion, open heart surgery, transplantation) and thus may contribute significantly to morbidity among patients with coronary artery
disease. In recent years an increasing number of studies have provided indirect evidence that postischemic myocardial dysfunction may be
mediated in part by the generation of reactive oxygen species, such as superoxide radical (.O2), hydrogen peroxide
(H2O2) and hydroxyl radical (.OH). Thus, it has been shown that the recovery of the stunned myocardium is enhanced by
agents that either scavenge oxygen metabolites, such as superoxide dismutase and catalase, N-2-mercaptopropionylglycine and dimethylthiourea,
or prevent their generation, such as allopurinol, oxypurinol and desferrioxamine. More recent experiments utilizing electron paramagnetic
resonance spectroscopy have directly demonstrated that reperfusion after a reversible ischemic episode is associated with a burst of free r
adical production. At present, the evidence supporting the free radical hypothesis is suggestive but not conclusive. Definitive demonstration
of the role of oxy-radicals will require careful studies measuring the production of these species in conscious animal models of postischemic
dysfunction. If confirmed, the free radical hypothesis will provide not only new important insights into the pathophysiology of ischemic
injury, but also a rationale for developing clinically applicable interventions.

Looking for an effective antioxidant to control excessive free radicals?
Consider Osumex Flax Hulls which has a high
ORAC value of 19,600 and a powerful antioxidant. It is also a most nutritious fibre!

**ORAC (Oxygen Radical Absorbance Capacity) is a method of measuring antioxidant capacities of different foods

Osumex Free Radical Test kit - see sample kit below

Malondialdehyde (MDA) is a by-product of free radical activity and this is what the test kit measures.

It is recommended that you test at least once a week, if excessive free radical activity is found, until it is brought under control, or
once a month or at least once every few months to make sure free radicals in the body are not running rampant!

The above information is provided for general
educational purposes only. It is not intended to replace competent
health care advice received from a knowledgeable healthcare professional.
You are urged to seek healthcare advice for the treatment of any
illness or disease.
Health Canada and the FDA (USA) have not evaluated these
statements. This product is not intended to diagnose, treat, cure, or prevent
any disease.